Universität zu Köln

Michely, Jochen, Volz, Lukas J. ORCID: 0000-0002-0161-654X, Barbe, Michael T., Hoffstaedter, Felix ORCID: 0000-0001-7163-3110, Viswanathan, Shivakumar ORCID: 0000-0002-7513-3778, Timmermann, Lars, Eickhoff, Simon B. ORCID: 0000-0001-6363-2759, Fink, Gereon R. ORCID: 0000-0002-8230-1856 and Grefkes, Christian ORCID: 0000-0002-1656-720X (2015). Dopaminergic modulation of motor network dynamics in Parkinson's disease. Brain, 138. S. 664 - 679. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

Although characteristic motor symptoms of Parkinson's disease such as bradykinesia typically improve under dopaminergic medication, deficits in higher motor control are less responsive. We here investigated the dopaminergic modulation of network dynamics underlying basic motor performance, i.e. finger tapping, and higher motor control, i.e. internally and externally cued movement preparation and selection. Twelve patients, assessed ON and OFF medication, and 12 age-matched healthy subjects underwent functional magnetic resonance imaging. Dynamic causal modelling was used to assess effective connectivity in a motor network comprising cortical and subcortical regions. In particular, we investigated whether impairments in basic and higher motor control, and the effects induced by dopaminergic treatment are due to connectivity changes in (i) the mesial premotor loop comprising the supplementary motor area; (ii) the lateral premotor loop comprising lateral premotor cortex; and (iii) cortico-subcortical interactions. At the behavioural level, we observed a marked slowing of movement preparation and selection when patients were internally as opposed to externally cued. Preserved performance during external cueing was associated with enhanced connectivity between prefrontal cortex and lateral premotor cortex OFF medication, compatible with a context-dependent compensatory role of the lateral premotor loop in the hypodopaminergic state. Dopaminergic medication significantly improved finger tapping speed in patients, which correlated with a drug-induced coupling increase of prefrontal cortex with the supplementary motor area, i.e. the mesial premotor loop. In addition, only in the finger tapping condition, patients ON medication showed enhanced excitatory influences exerted by cortical premotor regions and the thalamus upon the putamen. In conclusion, the amelioration of bradykinesia by dopaminergic medication seems to be driven by enhanced connectivity within the mesial premotor loop and cortico-striatal interactions. In contrast, medication did not improve internal motor control deficits concurrent to missing effects at the connectivity level. This differential effect of dopaminergic medication on the network dynamics underlying motor control provides new insights into the clinical finding that in Parkinson's disease dopaminergic drugs especially impact on bradykinesia but less on executive functions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Michely, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Volz, Lukas J. UNSPECIFIED orcid.org/0000-0002-0161-654X UNSPECIFIED Barbe, Michael T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffstaedter, Felix UNSPECIFIED orcid.org/0000-0001-7163-3110 UNSPECIFIED Viswanathan, Shivakumar UNSPECIFIED orcid.org/0000-0002-7513-3778 UNSPECIFIED Timmermann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Eickhoff, Simon B. UNSPECIFIED orcid.org/0000-0001-6363-2759 UNSPECIFIED Fink, Gereon R. UNSPECIFIED orcid.org/0000-0002-8230-1856 UNSPECIFIED Grefkes, Christian UNSPECIFIED orcid.org/0000-0002-1656-720X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-406688
DOI:	10.1093/brain/awu381
Journal or Publication Title:	Brain
Volume:	138
Page Range:	S. 664 - 679
Date:	2015
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2156
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BASAL GANGLIA; EFFECTIVE CONNECTIVITY; EXECUTIVE DYSFUNCTION; DIAGNOSTIC-CRITERIA; EXTERNAL CUES; REACTION-TIME; LEVODOPA; FMRI; MOVEMENT; PERFORMANCE Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40668